An Alternative Promoter in the Mouse Major Histocompatibility Complex Class II I-Aβ Gene: Implications for the Origin of CpG Islands

Abstract

Nonmethylated CpG islands are generally located at the 5′ ends of genes, but a CpG island in the mouse major histocompatibility complex class II I-Aβ gene is remote from the promoter and covers exon 2. We have found that this CpG island includes a novel intronic promoter that is active in embryonic and germ cells. The resulting transcript potentially encodes a severely truncated protein which would lack the signal peptide and external β₁ domains. The functional significance of the internal CpG island may be to facilitate gene conversion, thereby sustaining the high level of polymorphism seen at exon 2. Deletions of the I-Aβ CpG island promoter reduce transcription and frequently lead to methylation of the CpG island in a transgenic mouse assay. These and other results support the idea that all CpG islands arise at promoters that are active in early embryonic cells.